Interferon and Risk for Drug-Seeking Behavior

摘要

Interferon (IFN), a biological medication used to treat viral hepatitis and certain cancers, has clinically significant potential to cause a wide range of adverse neuropsychiatic effects. The spectrum ranges from agitation, aggression, insomnia and irritability, to suicidal thought and drug-seeking behavior (DSB). Out of a total population of 353 patients infected with hepatitis C virus (HCV), 132 patients at an inner city hepatitis clinic underwent treatment. Those treated were questioned at intake and on a regular basis for the initiation or increase of DSB. In addition, when warranted, patients were tested for the presence of drugs they were not prescribed. Over a four year period, ten patients (4 currently receiving treatment with IFN, 4 with prior treatment, and 2 who never received IFN) reported an increase in DSB. The danger of developing IFN-induced DSB appears to be relatively low (< 3%) in our patient population, and we also observed DSB in HCV patients who were not treated with IFN. To our knowledge, this is the first study of the incidence of DSB associated with IFN treatment for HCV that completely surveyed the HCV-treated population and used urine toxicology to verify illicit drug use. Introduction Patients with DSB have an inappropriate focus on obtaining a desired abused drug, i.e. cocaine, opioids, methamphetamine, etc. without concern of other more appropriate issues, such as diagnosis or treatment of their addictive behavior (Vissers, 2002). DSB includes abused drug preoccupation (talk and memories), and the craving and actual search for and use of abused drugs. It may be true that DSB as an observed action may not always be preceded by drug-related thoughts and memories as associated cognitive activity. However, it is likely that in most cases these cognitive activities precede DSB as action. Since DSB and use has the potential for dire consequences to IFN therapy in the treatment of HCV, we have questioned for the self-report of such drug abuse-related cognitive activity in regular office visits. As a general rule, it is reasonable to urge patients to avoid any stimulus to DSB while undergoing treatment for viral hepatitis, because of the potentially harmful effects of non-prescribed and addictive medication on antiviral therapy. Since the principle routes of contraction of infection for HCV include injection drug use (IDU), any increase in DSB caused by a side effect of a therapeutic (such as IFN) could become counter-therapeutic. IDU is known to suppress the immune system in some [for example, HIV] viral infections (Thompson & Salvato, 1998). Even though frequent illicit drug use during treatment of HCV may lead to decreased adherence (Sylvestre & Clements, 2007 ), several researchers (Robaeys & Buntinx, 2005); (Sylvestre, Litwin, Clements, & Gourevitch, 2005); (Sylvestre & Clements, 2007 ); (Grebely et al., 2007 ) have reported that illicit drug use itself may not counter the therapeutic response to IFN. Although the Warnings Section, Neuropsychiatric Subsection of the prescribing information (PI) for pegylated interferon alpha 2 (IFN) mentions that “relapse of drug addiction” may occur in patients, no specific information is given on the frequency of occurrence, the causal relatedness or predisposing or inciting factors. Upon query to the manufacturers, they were not able to supply specific data in these areas. A search of Medline also did not reveal specific published information in this regard. The aim of this observational study was to determine the incidence of DSB in a population being treated for HCV in a inner city community hospital, using standardized and previously validated approaches. Methodology Three hundred fifty three patients with HCV were evaluated for treatment at the Hepatitis Clinic of Cooper Green Mercy Hospital (CGMH), an inner city safety net medical facility in Birmingham, Alabama. Patients did not automatically receive antidepressants as a prophylactic action prior to therapy